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Human Leukocyte Antigens (HLA) and HIV Disease Progression

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The link between HLA types and HIV disease progression has been known for over a decade now from, among others, analyses of data from the Multi-Center AIDS Cohort (MACS). McMichael and colleagues have also documented CTL escape through the mutation of viral peptides which are to be "presented" by HLA class I (A, B, C) to the immune system (CD8 cells). More recently it has been shown that HLA class I alleles B27 and B57 are associated with better disease prognosis, while others (such as B35) are associated with worse outcome. The mechanism by which HLA influences disease progression is not yet understood. Some researchers have suggested that particular HLA molecules may be directly involved in restricting HIV replication, although more research is needed to understand this process.

The human leukocyte antigens (HLAs) are also known as MHC (major histocompatiblity complex) or "self" molecules. They are genetically inherited proteins present on the surface of human cells. T and B cells recognize antigens only when "presented" to them next to an MHC ("self") molecule. There are two main types of HLA. Class I is divided into HLA A, B, C and are expressed by most human cells. Class I HLAs are involved in presenting antigen to CD8 cells, thus activating the CD8s. When CD8 cells recognize antigen presented by HLA class I, they kill the cell presenting it. In this way the CD8 cells destroy cells infected with viruses, including HIV. Genetic make-up of a person's HLA affects the rate of HIV disease progression.

Class II is divided into HLA DP, DQ, DR and are expressed by macrophages and dendritic cells. Class II is involved in presenting antigen to CD4 cells, thus activating CD4 cells. When CD4 cells recognize antigen presented by HLA class II, they secrete cytokines (e.g., IL-2, IL-4) which in turn stimulate further immune responses. Mass General's Bruce Walker, the godfather of structured treatment interruption in acute HIV infection, argues that the role of particular alleles in the loss of control in persons who experience viral breakthrough on antiretroviral therapy needs to be carefully studied. Similarly, he says it is important to determine whether early treatment of acute infection followed by STI "can ever result in durable control in someone with a 'disadvantageous allele.'"